Due to their anatomic, physiologic, developmental, and behavioral characteristics, children are particularly vulnerable to bioterrorism agents. The symptoms associated with most bioterrorism agents can be difficult to differentiate from common childhood illnesses, as most biological weapons are associated with clinical presentations that mimic nonspecific febrile illnesses. It is extremely important that emergency clinicians are able to recognize unusual illness patterns that could distinguish a natural outbreak from a bioterrorism attack. This issue reviews the highest-risk bioterrorism agents and provides guidance for diagnosing and managing pediatric patients who have been exposed to these agents. You will learn:

• Which pediatric-specific characteristics make children more vulnerable to bioterrorism agents
• How to distinguish a natural disease outbreak from a bioterrorism attack
• Where to find online resources that can provide support during a bioterrorism crisis
• Common presentations associated with the CDC Category A bioterrorism agents: anthrax (Bacillus anthracis), botulism (Clostridium botulinum toxin), plague (Yersinia pestis), smallpox (Variola major), tularemia (Francisella tularensis), viral hemorrhagic fevers (filoviruses [eg, Ebola, Marburg] and arenaviruses [eg, Lassa, Machupo])
• Preferred treatment and postexposure prophylaxis for children who have been exposed to Category A bioterrorism agents

Abstract

Due to their anatomic, physiologic, developmental, and behavioral characteristics, children are particularly vulnerable to bioterrorism agents. Symptoms associated with most bioterrorism agents can be difficult to differentiate from common childhood illnesses. It is extremely important that emergency clinicians are able to recognize unusual illness patterns that could distinguish a natural outbreak from a bioterrorism attack. Resources available through government agencies and leading pediatric organizations can aid in diagnosis and treatment. This issue reviews the highest-risk bioterrorism agents and provides guidance for diagnosing and managing pediatric patients who have been exposed to these agents.

Case Presentations

During a busy flu season, a 5-year-old previously healthy boy presents to the ED after 2 days of fever, cough, fatigue, and myalgias. He is given an antipyretic in triage. The patient is up-to-date on his vaccine schedule and has had an influenza vaccine this season. He has an episode of nonbilious emesis while waiting to be seen. In the process of being reassessed by the triage nurse, the patient is noted to have significant dyspnea and an oxygen saturation of 89%. The boy’s vital signs are: temperature, 35.6°C (96.0°F); heart rate, 178 beats/min; respiratory rate, 44 breaths/min; and blood pressure, 70/30 mm Hg. The child becomes pale and diaphoretic. A sepsis alert is triggered, and the patient is taken back to a room. On further questioning, the mother reports no notable sick contacts; she also states that the child has not had nasal congestion or a runny nose. You note a pale, listless child and auscultate diffuse crackles at the lower lung bases. You suspect this child will need critical-level care and, given the busy influenza season, you call your critical care colleague who exclaims, “Another one—this is the seventh patient with a similar presentation in 24 hours! What is going on?”

Your next patient is a 2-year-old girl with a 3-day history of high fevers, body aches, fatigue, and a rash. Her vital signs are; temperature, 40.5°C (104.9°F); heart rate, 105 beats/min; and blood pressure, 100/60 mm Hg. The physical examination reveals pustular vesicles with central umbilication in the same stage of development on her face, torso, and extremities. The mother says the lesions started in the girl's mouth 3 to 4 days ago. The patient's past medical history is notable only for severe eczema.

What features of these illnesses suggest a potential bioterrorism threat? What patient(s) require isolation? What public health notifications are needed?

Introduction

Following the 2001 anthrax attacks in the United States, in which 5 people died and 17 were infected, there has been increased surveillance for unusual disease patterns associated with biological weapons.1-3 A biological weapon is defined as any microorganism or its toxin that can be found in nature and used to intentionally cause significant morbidity or mortality. The United States Centers for Disease Control and Prevention (CDC) ranks bioterrorism agents according to the potential threat to national security. This is determined by the agent’s ability to be easily disseminated, cause high mortality, or cause significant public panic. The most dangerous biological agents are easy to acquire, process, and deliver and have a low infective dose. The largest reported act of bioterrorism in the United States was in 1984, when Salmonella typhimurium was used by a religious commune to intentionally contaminate salad bars in Oregon restaurants.4 Internationally, at least 17 nations are believed to have biological weapons programs with offensive capabilities.5 Globally, of 191 bioterrorism threats identified over the past century, more than half were anthrax threats, and the majority used aerosolized spores.6

In response to the anthrax attacks of 2001, the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 mandated the United States Department of Health and Human Services (HHS) to maintain and regulate a list of biological agents and toxins that have the potential to threaten public health and safety.7 The ability to distinguish the intentional use of pathogens and toxins to inflict harm from naturally occurring disease outbreaks relies on knowledge about the ecologic and biologic characteristics of the pathogen, the route of infection, the epidemiology of the outbreak, and the mode of dissemination.8-10 Typically, natural events cannot reproduce the overwhelmingly massive exposures that can be created in a terrorist scenario.11

The symptoms associated with most bioterrorism agents can be difficult to differentiate from common childhood illnesses, as most biological weapons are associated with clinical presentations that mimic nonspecific febrile illnesses. The febrile child is one of the most common presentations in the emergency department (ED), which increases the challenge of distinguishing a naturally occurring illness from a bioterrorism threat. Although children represent approximately 25% of the population in the United States, they are often disproportionately affected by disasters and public health emergencies,12 due to their unique anatomic, physiologic, developmental, and behavioral characteristics.13(See Table 1.) Drugs used to treat most biological warfare agents have not been tested or used extensively in pediatric populations, and would likely be issued under an emergency use authorization or an investigational new drug protocol. Lack of pediatric expertise, equipment, or disaster planning that included children could exacerbate the potential harms inflicted on pediatric victims of a bioterrorism attack.

To the average clinician, bioterrorism may seem like a remote possibility, but emergency clinicians are on the front lines of managing individuals or groups of patients affected by a biological agent.14 It is imperative that emergency clinicians be vigilant about identifying and understanding the management of unusual disease outbreaks that may result from biological weapons. How does one discern a unique event in a vulnerable host with a nonspecific presentation? There are many resources that are available through government agencies and leading pediatric organizations, and understanding how to access and apply these resources for real-time use is essential. (See Table 2.) The more knowledgeable emergency clinicians are about bioterrorism agents, the greater the likelihood of recognition.15,16 Also important is a level of comfort in knowing when and how to report suspicions of bioterrorism to local public health and law enforcement agencies.17

This issue of Pediatric Emergency Medicine Practice outlines priorities in the ED management of the pediatric victim of a bioterrorism agent. This review will focus on the highest-risk agents identified by the CDC, referred to as Category A agents. (See Table 3.) Key questions that are addressed include:

What features of an infectious outbreak distinguish it as a bioterrorism event?

Why are children more vulnerable to bioterrorism agents?

What resources are available to assist with a bioterrorism crisis?

Who should be notified if there is concern for bioterrorism?

How are bioterrorism agents diagnosed and treated in children?

Which patients require decontamination, isolation, or quarantine?

What can be done to protect hospital staff from potential exposure?

Risk Management Pitfalls in the Management of Suspected Bioterrorism in the Pediatric Patient

2. “If a bioterrorism patient shows up, I will be able to rely on the infectious disease and infection control teams for recommendations.”

Recognizing suspicious illness patterns is an important responsibility of front-line emergency clinicians. While infectious disease and infection control specialists provide specific expertise, the protection of patients and staff depends on adherence to recommended protocols as early as possible.

6. “Managing a surge from a bioterrorism event is similar to managing a mass casualty. We should be able to use similar protocols”

Bioterrorism agents are often highly contagious and require public health support beyond the scope of any single healthcare facility. Specific protocols are important to best recognize and respond to the threat of bioterrorism.

8. “Yes, there has been a spike in pneumonic tularemia in the ED, but it’s endemic to this area, so that shouldn’t be cause for concern.”

Any unusual cluster of presentations of Category A bioterrorism agents should be cause for concern. The inhalational form of any Category A illness should also be a red flag, as the aerosolized form of these agents is the most likely mechanism used for a bioterrorism attack.

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of patients. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study is included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the author, are highlighted.

Grunow R, Finke EJ. A procedure for differentiating between the intentional release of biological warfare agents and natural outbreaks of disease: its use in analyzing the tularemia outbreak in Kosovo in 1999 and 2000. Clin Microbiol Infect. 2002;8(8):510-521. (Review)

Children are particularly vulnerable to bioterrorism agents, due to their smaller size, developmental immaturity, behavioral characteristics, increased minute ventilation, and decreased physiologic reserve.

The symptoms associated with most bioterrorism agents can be difficult to differentiate from those of common childhood illnesses, as most biological weapons are associated with clinical presentations that mimic nonspecific febrile illnesses.

The United States Centers for Disease Control and Prevention (CDC) has designated the highest-risk bioterrorism agents as Category A agents. Diseases caused by these agents include, anthrax, botulism, plague, smallpox, tularemia, and viral hemorrhagic fevers.

Anthrax (Bacillus anthracis) can infect patients via 3 routes of infectivity, depending on where the spores deposit: (1) cutaneous, (2) inhalational, and (3) gastrointestinal. The inhalational form is the form most associated with bioterrorism and should be considered in the setting of mediastinitis demonstrated by fever, shortness of breath, chest pain, and a widened mediastinum with pleural effusions on chest x-ray.

CME Information

Discuss the Category A bioterrorism agents and their clinical presentations in pediatric patients

Describe the treatment and prophylaxis recommendations for Category A bioterrorism agents

Discuss the public health reporting recommendations for Category A bioterrorism agents

CME Information

Date of Original Release: December 1, 2018. Date of most recent review: November 15, 2018. Termination date: December 1, 2021.

Accreditation: EB Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. This activity has been planned and implemented in accordance with the accreditation requirements and policies of the ACCME.

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